Mixed anhydrides of n-aroyl-1-(lower alkyl)-5-nitro-2-imidazolecarboximidic acid and benzoic acids

ABSTRACT

This disclosure describes compounds of the class of mixed anhydrides of N-aroyl-1-(lower alkyl)-5-nitro-2imidazolecarboximidic acid and a benzoic acid useful as intermediates for the preparation of certain antibacterial and antiprotozoal agents.

United States Patent Papaioannou 1 June 27, 1972 [54] MIXED ANHYDRIDES OF N-AROYL-l- (LOWER ALKYL)-5-NITRO-2- IMIDAZOLECARBOXIMIDIC ACID AND BENZOHC ACIDS 21 Appl. No.: 29,653

[52] US. Cl ..260/309, 260/240 A, 260/3068 D,

260/999 [51] Int. Cl. ..C07d 49/36 [58] Field of Search ..260/309, 347.4

[56] References Cited UNITED STATES PATENTS 3,272,828 9/1966 von Esch et al ..260/347.4

FOREIGN PATENTS OR APPLICATIONS 963,561 7/1964 Great Britain ..260/347.4

OTHER PUBLICATIONS Merck Chem. Abst. Vol. 63, columns 608-9 (1965). QD1.A5I Walters et al. J. Org. Chem. Vol. 26, pages 1161-4 (1961). QD241.J6

von Esch et al ..260/347.4

Primary Examiner-Natalie Trousof Att0rneyEdward A. Conroy, Jr.

[5 7] ABSTRACT This disclosure describes compounds of the class of mixed anhydrides of N-aroyl-l-(Iower a1kyl)-5-nitro-2-imidazolecarboximidic acid and a benzoic acid useful as intermediates for the preparation of certain antibacterial and antiprotozoal agents.

9 Claims, No Drawings BRIEF SUMMARY OF THE INVENTION This invention relates to new organic compounds and, more particularly, is concerned with novel mixed anhydrides of N- aroyll lower alkyl )-5nitro-2-imidazolecarboximidic acids and benzoic acids which may be represented by the following structural formula:

wherein R is lower alkyl and R and R are the same or different and are each phenyl or para-substituted phenyl. Suitahlc lower alkyl groups contemplated by the present invention are those having up to four carbon atoms such-as, for example, methyl, ethyl, n-propyl, iso-butyl, sec-butyl, etc. Suitable parasubstituted phenyl groups contemplated by the present invention are, for example, p-tolyl, p-chlorophenyl, p-bromophenyl, p-nitrophenyl, p-methoxyphenyl, p-acetoxyphenyl, pacetylphenyl, p-acetamidophenyl, and the like.

DETAILED DESCRIPTION OF THE INVENTION l l OZN C0 Rz I? I C-Ri I R g R 7 v wherein R, R, and R are as hereinabove defined and X is chloro or bromo. As set forth above, condensation of a 1- (lower alkyl)-2-methyl-5-nitroimidazole (IV) with an aroyl halide (R,COX) affords the corresponding benzoate or parasubstituted benzoate ester of l-(lower alkyl)--nitro-a-aryl-2- imidazoleethenol (III). This condensation is best carried out in an inert solvent such as tetrahydrofuran, diglyme, toluene, and the like in the presence of a tertiary amine such as trimethylamine, triethylamine, or diisopropylethylamine at a temperature of about to 125 C. for a period of time of l624 hours. From about 2 to about 2.5 mole equivalents of the aroyl halide (R COX) are preferably employed and a sufficient amount of tertiary amine is used to both catalyze the reaction and to react with the hydrogen halide produced.

The 1-( lower alkyl)-5nitroa-aryl-2-imidazoleethenol arylcarboxylate III) is converted to the corresponding l-oximinol-[ l-(lower alkyl)-5nitro-2-imidazolyl]-2-arylglyoxal (II) by hydrolysis to the intermediate l-(lower alkyl)-5-nitro-a-aryl-2 imidazoleethenol (not isolated) followed by nitrosation in situ. The hydrolysis step is best carried out in aqueous ethanol (III) l (1) hydrolysis RzCOX (2) nitrosation O l J r OZN C- R! as solvent with a strong mineral acid (e.g., cone. hydrochloric, conc. sulfuric, etc.) at the reflux temperature for a period of time of 4-8 hours. The resulting solution is cooled to l020 C. and nitrosation is accomplished by adding an aqueous solution of sodium nitrite or potassium nitrite and stirring the reaction mixture at about room temperature for a period of time of 3-6 hours.

The so obtained l-oximino-1-[ l-(lower alkyl)-5-nitro-2- imidazolyl]-2-arylglyoxal (II) is converted to the corresponding mixed anhydride of N-aroyl-l-( lower alkyl)-5-nitro-2- imidazolecarboximidic acid and a benzoic acid (I) by treatment with an aroyl halide (R COX). The conversion of (II) to (I) is best carried out in an inert solvent such as acetonitrile, nitromethane, dimethylformamide, ethyl acetate, benzene, toluene, o-dichlorobenzene, etc. (although great excess of the aroyl halide may also serve as the solvent. if desired) at a temperature of about 25 to 150 C, preferably at a temperature of from about 60 C. to about 100 C. The reaction generally requires from about 30 minutes to 2 hours for completion but this time may be extended if desired. It is usually found to be practical to conduct the reaction employing a stoichiometric excess of the aroyl halide (R COX) reactant. A slight excess is generally sufficient to give optimum product yields but on occasion it may be desirable to employ a large excess, for example, 2 or 3 mole equivalents of aroyl halide (R COX) per mole of (II). Larger excesses of aroyl halide may be used but there is generally no advantage to be gained in product yield.

The novel compounds of the present invention (1) are useful as intermediates for the preparation of certain 2-amino-5-[ 1- (lower alkyl)-5-nitro-2-imidazolyl]-l,3,4-thiadiazoles (VI) in accordance with the following reaction scheme:

I l OZN o-o- Ra base in a lower alkanol solvent (e.g., methanol, ethanol,

isopropanol, n-butanol, etc.) at a temperature of from about 0 C. to about 100 C., preferably 2030 C., for a period of time of a few hours or more. Suitable strong bases are, preferably, alkali metal hydroxides, cyanides, or alkoxides such as sodium hydroxide, potassium hydroxide, potassium cyanide, sodium cyanide, potassium tert-butoxide, sodium methoxide, sodium ethoxide, and the like. While only a cata- I lytic amount of base in excess of and in addition to a stoichiometric equivalent is required for the reaction, two or even three mole equivalents of base may be employed. However, larger excesses of strong base do not appear to have any advantage. In carrying out the second step of the conversion of (I) to (V), there is added to the reaction mixture from the first step an equimolar amount of a thiosemicarbazide of the formula:

wherein R and R are as hereinabove defined. An amount of an organic carboxylic acid such as acetic, benzoic, propionic, butyric, etc. is added sufiicient to first neutralize the reaction mixture and then provide a catalytic or greater amount of the acid. This second step is then carried out at a temperature of from about C. to about 100 C., preferably 20-30 C. for a period of time of a few hours or more. Alternatively, a catalytic amount of a strong mineral acid or strong organic acid, such as benzene sulfonic acid or trifluoroacetic acid, may be used provided the temperature is held between about 0 C. and about 30 C. The product (V) is removed by filtration, treated with sodium bicarbonate solution, washed, and dried.

The cyclization of the intermediate l-[l-(lower alkyl)-- nitro-2-imidazolecarboximidoyl]-3-thiosemicarbazides (V) to the corresponding 2-amino-5-[ l-(lower alkyl)-5-nitro-2- imidazolyl]-l,3,4-thiadiazoles (VI) is accomplished by means of a strong mineral acid or strong organic acid in a lower alkanol (e.g., methanol, ethanol, isopropanol, etc.) as solvent. Suitable mineral acids which may be employed are, for example, conc. hydrochloric, conc. hydrobromic, conc. sulfuric, and the like. Among the strong organic acids that can be used are p-toluenesulfonic acid, trifluoroacetic acid, and the like. The reaction is best carried out at a temperature of from about 45 C. to about 150 C., conveniently at the reflux temperature, for a period of about an hour, more or less. The product (Vl), which separates from the reaction mixture, is removed by filtration, washed, and dried. The 2-amino-5-[ l-(lower alkyl)-5-nitro-2-imidazolyl]-l ,3,4-thiadiazoles (VI) are useful as antibacterial and antiprotozoal agents as is more fully set forth in U.S. Pat. No. 3,452,035 to Berkelhammer et al.

The invention will be described in greater detail in conjunction with the following specific examples.

EXAMPLE 1 Preparation of l-methyl-5-nitro-a-phenyl-2-imidazoleethenol benzoate Trimethylamine, 33.8 grams, 0.573 mole, is dissolved in 120 ml. of toluene. The solution is mixed with 20 grams, 0.141 mole, of l,2-dimethyl-5-nitroimidazole and 41 ml., 0.354 mole, of benz oyl chloride. The reaction mixture is stirred at about 25 C. for about hours. The resulting bright yellow precipitate is filtered, mixed with 100 ml. of water, refiltered, washed with water, and dried. There is obtained 47.7 grams, 97 percent, of l-methyl-5-nitro-a-phenyl-2-imidazoleethenol benzoate, m.p. 205207 C.

EXAMPLE 2 Preparation of l-ethyl-5-nitro-a-phenyl-2-imidazoleethenol benzoate The procedure of Example I is repeated, substituting an equimolar amount of l-ethyl-2-methyl-5-nitroimidazole for the l ,2-dimethyl-S-nitroimidazole employed in that example. There is thus obtained the l-ethyl-5-nitro-a-phenyl-2- imidazoleethenol benzoate.

EXAMPLE 3 Preparation of l-ethyl-5-nitro-a-(p-tolyl)-2-imidazoleethenol p-toluate By replacing the benzoyl chloride employed in Example 2 with an equimolar quantity of p-toluyl chloride and following substantially the same procedure of Example 2, there is obtained the l-ethyl-5-nitro-a-(p-tolyl)-2-imidazoleethenol ptoluate.

EXAMPLE 4 Preparation of l-isopropyl-5-nitro-a-(p-chlorophenyl)-2- imidazoleethenol p-chlorobenzoate Following the general procedure of Example 1, l-isopropyl- 2-methyl-5-nitroimidazole is treated with p-chlorobenzoyl chloride to give the l-isopropyl-5-nitro-a-( p-chlorophenyl )-2- imidazoleethenol p-chlorobenzoate.

EXAMPLE 5 Preparation of l-isobutyl-5-nitro'a-( p-acetoxyphenyl )-2- imidazoleethenol p-acetoxybenzoate Following the general procedure of Example l, l-isobutyl- Z-methyl-S-nitroimidazole is treated with p-acetoxybenzoyl bromide to give the l-isobutyl-5-nitro-a-(p-acetoxyphenyl)-2- imidazoleethenol p-acetoxybenzoate.

EXAMPLE 6 Preparation of 1-oximino-l-( l-methyl-5-nitro-2-imidazolyl)-2 -phenylglyoxal I A mixture of 60 grams, 0.172 mole, of l-methyl-S-nitro-aphenyl-2-imidazoleethenol benzoate, 240 ml. of water, 240 ml. of ethanol, and 200 ml. of 37 percent hydrochloric acid is refluxed for 6 hours. The resulting solution is allowed to cool to room temperature and then cooled in an ice bath to l720 C. A solution of 35 grams, 0.507 mole, of sodium nitrite in ml. of water is added slowly over a period of about 1 hour, maintaining the temperature between about l7-20 C. The resulting suspension is stirred at about room temperature for 5 hours, the product is filtered, washed with 500 ml. of water, then 75 ml. of acetone, and dried. There is obtained 41.7 grams, 89 percent, of l-oximino-l-( l-methyl-5-nitro-2- imidazolyl)-2-phenylglyoxal, m.p. l87l 88 C. (dec.).

EXAMPLE 7 Preparation of l-oximino-l-( l-ethyl-5-nitro-2-imidazolyl )-2 -phenylglyoxal In place of the l-methy|-5-nitro-a-phenyl-2- EXAMPLE 8 Preparation of l-oximinol l-ethyl-5-nitro-2-imidazolyl )-2 -(p-tolyl)glyoxal The procedure of Example 6 is repeated, substituting .an equimolar amount of l-ethyl-5-nitro-a-(p-tolyl)-2- imidazoleethenol p-toluate for the l-methyl-5-nitro-a-phenyl- Z-imidazoleethenol benzoate employed in that example. There is thus obtained the 'l-oximino-l-(l-ethyl-5-nitro-2- imidazolyl)-2-(p-tolyl)glyoxal.

EXAMPLE 9 Preparation of l-oximino-l-( l-isopropyl-5-nitro-2- imidazolyl)- 2-(p-chlorophenyl)glyoxal By replacing the l-methyl-5-nitro-a-phenyl-Z- imidazoleethenol benzoate employed in Example 6 with an equimolar quantity of l-isopropyl-5-nitro-a-(p-chlorophenyl)-2-imidazoleethenol p-chlorobenzoate and following substantially the same procedure described in Example 6, there is obtained the l-oxirnino-l-'( l-isopropyl-5-nitro-2-imidazolyl)- 2-(p-chlorophenyl)glyoxal.

EXAMPLE 10 Preparation of l-oximinol l-isobutyl-5-nitro-2-imidazolyl) -2-(p-acetoxyphenyl)glyoxal Following the general procedure of Example 6, l-isobutyl- S-nitro-a-(p-acetoxyphenyl)-2-imidazoleethenol p-acetoxybenzoate is hydrolyzed and nitrosated to give the l-oximinol-( l-isobutyl-5-nitro-2-imidazolyl )-2-( p-acetoxyphenyl)glyoxal.

EXAMPLE 1 1 EXAMPLE 12 Preparation of the mixed anhydride of N-benzoyl-l-methyl-S- nitro 2-imidazolecarboximidic acid and benzoic acid A mixture of 5.00 grams, 0.0182 mole, of l-oximino-l-( lmethyl-S-nitro-2-imidazolyl)-2-phenylglyoxal, 3.2 ml., 0.0274,

mole, of benzoyl chloride, and 30 ml. of acetonitrile is refluxed for 2 hours. The reaction mixture is cooled, filtered, washed twice with methanol and dried. There is obtained 6.57 grams, 95 percent, of the mixed anhydride, m.p. 222224 C.

EXAMPLE 1 3 Preparation of the mixed anhydride of N-benzoyl-l-methyl-S- nitro -2-imidazolecarboximidic acid and 4-nitrobenzoic acid This compound is prepared by the method described in Example l2. From 5.00 grams of l-oximino-l-( l-methyl-S-nitro- 2-imidazolyl)-2-phenylglyoxal and 5.08 grams of 4- nitrobenzoyl chloride is obtained the mixed anhydride of N- benzoyl-l-methyl-5-nitro-2-imidazolecarboximidic acid and 4-nitrobenzoic acid, m.p. 2l42l5 C.

EXAMPLE 14 Preparation of the mixed anhydride of N-benzoyl-l-methyl-S- nitro -2-imidazolecarboximidic acid and 4-methoxybenzoic acid This compound is prepared by the method described in Example 12. From 5.00 grams of l-oximino-1-( l-methyl-S-nitro- 2-imidazolyl)-2-phenylglyoxal and 4.67 grams of anisoyl chloride is obtained the mixed anhydride of N-benzoyllmethyl-5-nitro-2-imidazolecarboximidic acid and 4-methoxybenzoic acid, m.p. 20l-203 C.

EXAMPLE 15 Preparation of the mixed anhydride of N-benzoyl-l-ethyl-S- nitro -2-imidazolecarboximidic acid and benzoic acid The procedure of Example ll is repeated, substituting an equimolar amount of l-oximino-l-( l-ethyl-5-nitro-2- imidazolyl)-2-phenylglyoxal for the 1-oximino-l-( l-methyl-S- nitro-2-imidazolyl)-2-phenylglyoxa1 employed in that example. There is thus obtained the mixed anhydride of N-benzoyl- 1-ethyl-5-nitro-2-imidazolecarboximidic acid and benzoic acid.

EXAMPLE 16 Preparation of the mixed anhydride of N-(p-toluyl)-l-ethyl-5 -nitro-2-imidazolecarboximidic acid and p-bromobenzoic acid Following the general procedure of Example 12, l-oximinol-( l-ethyl-5-nitro-2-imidazolyl)-2-(p-tolyl)glyoxal is treated with p-bromobenzoyl bromide to give the mixed anhydride of N -(p-toluyl l -ethyl-5 -nitro-2-imidazolecarboximidic acid and p-bromobenzoic acid.

EXAMPLE 17 Preparation of the mixed anhydride of N-(p-chlorobenzoyl)- l-isopropyl-S-nitro-Z-imidazolecarboximidic acid and pacetylbenzoic acid Following the general procedure of Example 12, l-oximino- 1-( l-isopropyl-5-nitro-2-imidazolyl )-2-( p-chlorophenyl)glyoxal is treated with p-acetylbenzoyl bromide to give the mixed anhydride of N-(p-chlorobenzoyl)-l-isopropyl-S-nitro Z-imidazolecarboximidic acid and p-acetylbenzoic acid.

EXAMPLE 1 8 Preparation of the mixed anhydride of N-(pacetoxybenzoyl l -isobutyl-5-nitro-2-imidazolecarboxirnidic acid and pacetamidobenzoic acid Following the general procedure of Example 12, l-oximinol-( 1-isobutyl-5-nitro-2-imidazolyl )-2-( p-acetoxyphen yl)glyoxal is treated with p-acetamidobenzoyl chloride to give the mixed anhydride of N-( p-acetoxybenzoyl)- l -isobutyl-5- nitro-2-imidazolecarboximidic acid and p-acetamidobenzoic acid.

EXAMPLE 19 Preparation of 1-(1-methyl-5-nitro-2- imidazolecarboximidoyl)-3 -thiosemicarbazide A mixture of 3.78 grams, 0.010 mole, of the mixed anhydride of N-benzoyl-l-methyl-5-nitro-2-imidazolecarboxirnidic acid and benzoic acid, 20 ml. of methanol and 0.81 gram, 0.015 mole, of sodium methoxide is stirred at room temperature for 2.5 hours. Thiosemicarbazide, 0.91 gram, 0.010 mole, and 1 ml. of glacial acetic acid are added and the mixture is stirred at room temperature for an additional 4 hours. The reaction mixture is then cooled in ice and filtered. The red-orange residue is slurried with a 20 percent solution of sodium bicarbonate and stirred for 1 hour, filtered, washed with water and methanol, and dried. There is obtained 1.70 grams of product, m.p. l8620l C. Recrystallization from a mixture of ethanol and dimethylformamide gives a product with a m.p. of 208-210 C. (dec.).

EXAMPLE 20 Preparation of 1-( l-methyl-5-nitro-2- imidazolecarboximidoyl)-4 -isopropyl-3-thiosemicarbazide Following the general procedure of Example 19, the mixed anhydride of N-benzoyl-1-methyl-5-nitro-2-imidazolecarboximidic acid and 4-nitrobenzoic acid is treated with 4- isopropyl-3-thiosemicarbazide to give the l-(l-methyl-S- nitro-2-imidazolecarboximidoyl)-4-isopropyl-B-thiosemicarbazide.

EXAMPLE 21 Preparation of l-( 1-methyl-5-nitro-2- in'1idazolecarboximidoyl)-4,4 -diethyl-3-thiosemicarbazide Following the general procedure of Example 19, the mixed anhydride of N-benzoyl-l-methyl-5-nitro-2-imidazolecarboximidic acid and 4-methoxybenzoic acid is treated with 4,4- diethyl-3-thiosemicarbazide to give the l-( l-methyl-5-nitro-2- imidazolecarboximidoyl)-4,4-diethyl-3-thiosemicarbazide.

EXAMPLE 22 orange residue is slurried with a 20 percent solution of sodium bicarbonate and stirred for about, 1 hour, filtered, washed thoroughly with water, then with 3 l-ml. portions of methanol and dried. There is obtained 1.65 grams of the title compound which, after recrystallization from a mixture of ethyl acetate and heptane, melts at 2267 C. (dec.).

EXAMPLE 23 Preparation of l-( l-ethyl--nitro-2-imidazolecarboximidoyl)- 4,4 -dimethyl-3-thiosemicarbazide Following the general procedure of Example 22, the mixed anhydride of N-( p-toluyl l -ethyl-5-nitro-2-imidazolecarboximidic acid and p-hromobenzoic acid is treated with 4,4- dimcthyl-3 -thioscmiczirhnzide to give the l-( l-ethyl-5-nitro-2- imiduzolcczirhoximidoyl )-4,4-dimethyl-3-thiosemicurbazide.

EXAMPLE 24 EXAMPLE 26 Preparation of 1-( l-isobutyl-5-nitro-2- imidazolecarboximidoyl) 4-ethyl-3-thiosemicarbazide Following the general procedure of Example 24, the mixed anhydride of N-(p-acetoxybenzoyl)-l-isobutyl-5-nitro-2- imidazolecarboximidic acid and p-acetamidobenzoic acid is treated with 4-ethyl-3thiosemicarbazide to give the l-(lisobutyl-S -nitro-2-imidazolecarboximidoyl )-4-ethyl-3- thiosemicarbazide.

EXAMPLE 27 Preparation of 2-amino-5-( l-methyl-5-nitro-2-imidazolyl)- -thiadiazole A mixture of 3.80 grams, 0.0156 mole, of l-( l-methyl-S- nitro-2-imidazolecarboximidoyl)-3-thiosemicarbazide, 30 ml. of methanol, and 12 ml. of 37 percent hydrochloric acid is refluxed for 1 hour, cooled in ice and filtered. The crystalline residue is suspended in 200 ml. of water, stirred for '2 hours, filtered, washed thoroughly with water, then with 4 l-ml. portions of methanol, and dried. There is obtained 2.93 grams of product, m.p. 262-264 C. (dec.).

EXAMPLE 28 The general procedure of Example 27 is repeated using a series of different starting materials. These starting materials and the corresponding products are set forth in the following table.

OQN N Starting material Product R R3 R4 l-(l-mcthyl-5-nitro-2-iinidazolccarboximidoyl)-4-isopropyl-3-thioscmicarbazide VIa CH3 H /CH3 ClI 1-(l-methyl-S-nitro 2-imidazolecarboximidoyl)'4.4-diethyl-3-thiosemicarbazide VIb CH3 czHs CzHa 1-(l-ethyl-5-nitro-2-imidazolecarboximidoyl)-3-thiosemicarbazide VIc C2H5 H H 1-(l-ethyl5-nitro-iZ-imidazolecarboximidoyl)-4,4-dimethyl-3-thioscmicarbazide. VId C2H5 CH CH3 1-(l-isop1opyl-5-nitro-2 imidazolecarboximidoyl)4-methyl-3-thiosemicarbazidm VIo /CH3 H CH:

v CH] 1-(l-isobutyl-S-nitro-Z-imidazolecarboximidoyl)-4-ethyl-3-thiosemicarbazide VIi CH3 H 02H! CHZCH EXAMPLE 29 ml. of water, and 4 l-ml. portions of methanol, and dried.-The red-orange residue is slurried with a 20 percent sodium bicarbonate solution, stirred for 1 hour, filtered, washed thoroughly with water and dried. There is obtained 2.5 grams of product m.p. l89-202 C. (dec.), which was recrystallized from a mixture of ethanol and dimethyl formamide to give a m.p. of

209-2 1 2 C. (dec.).

EXAMPLE 25 isopropyl-5-nitro-2-imidazolecarboximidoyl)-4-methyl-3- thiosemicarbazide.

Preparation of 2-amino5-( 1-methy1-5-nitro-2-imidazolyl)- 1,3,4 -thiadiazole A mixture of 40 ml. of methanol, 1.40 grams, 0.026 mole, of I sodium methoxide and 7.56 grams, 0.020 mole, of the mixed anhydride of N-benzoyl-S-nitro-2-imidazolecarboximidic acid and benzoic acid is stirred at room temperature for 3 hours. Thiosemicarbazide, 1.82 grams, 0.020 mole, and 3 ml. of glacial acetic acid are added and the reaction mixture is allowed to stir at room temperature for an additional 5 hours. Hydrochloric acid, 37 percent, 10 ml., is added and the mixture is refluxed for 1 hour, cooled and filtered. The crystalline residue is suspended in 200 ml. of a 20 percent solution of sodium bicarbonate, stirred for 2 hours, filtered, washed thoroughly with water, then with 4 l-ml. portions of methanol and dried. There is obtained 1.80 grams, of product which,

after recrystallization from dimethylformamide, melts at 264266 C. (dec.).

.1 claim:

1. A nitroimidazole of the formula:

2. The nitroimidaiole in accordance with claim 1 wherein R is methyl, R, is phenyl, and R is phenyl.

3. The nitroimidazole in accordance with claim 1 wherein R is methyl, R, is phenyl, and R is p-nitrophenyl.

4. The nitroimidazole in accordance with claim 1 wherein R is methyl, R, is phenyl, and R is p-methoxyphenyl.

5. The nitroimidazole in accordance with claim 1 wherein R is methyl, R, is p-nitrophenyl, and R is phenyl.

6. The nitroimidazole in accordance with claim 1 wherein R is ethyl, R, is phenyl, and R is phenyl.

7. The nitroimidazole in accordance with claim 1 wherein R is ethyl, R, is p-tolyl, and R is p-bromophenyl.

8. The nitroimidazole in accordance with claim 1 wherein R is isopropyl, R, is p-chlorophenyl, and R5 is p-acetylphenyl.

9. The nitroimidazole in accordance with claim 1 wherein R is isobutyl, R, is p-acetoxyphenyl, and R is p-acetamidophenyl. 

2. The nitroimidazole in accordance with claim 1 wherein R is methyl, R1 is phenyl, and R2 is phenyl.
 3. The nitroimidazole in accordance with claim 1 wherein R is methyl, R1 is phenyl, and R2 is p-nitrophenyl.
 4. The nitroimidazole in accordance with claim 1 wherein R is methyl, R1 is phenyl, and R2 is p-methoxyphenyl.
 5. The nitroimidazole in accordance with claim 1 wherein R is methyl, R1 is p-nitrophenyl, and R2 is phenyl.
 6. The nitroimidazole in accordance with claim 1 wherein R is ethyl, R1 is phenyl, and R2 is phenyl.
 7. The nitroimidazole in accordance with claim 1 wherein R is ethyl, R1 is p-tolyl, and R2 is p-bromophenyl.
 8. The nitroimidazole in accordance with claim 1 wherein R is isopropyl, R1 is p-chlorophenyl, and R2 is p-acetylphenyl.
 9. The nitroimidazole in accordance with claim 1 wherein R is isobutyl, R1 is p-acetoxyphenyl, and R2 is p-acetamidophenyl. 